Objectives: To build a high-performance, high-resolution quantitative PET/CT scanner dedicated to imaging the breast. This will permit validation of anato-metabolic imaging of the breast in the contexts of local staging, prediction of therapeutic response, follow-up for patients receiving conservative therapy and the development of new drugs for breast cancer treatment. Methods: Using a novel high-resolution, low-dead-time scintillation detector design using a dual-ended read-out scheme using APDs and PSPMTs, and a modified version of commercial PET electronics, we will build a PET scanner compact enough to fit inside the gantry of our existing breast CT scanner. We will combine the two devices to allow sequential imaging of the breast in the same clinical setting, resulting in accurately registered high-resolution functional and anatomic images. The device will be compatible with biopsy tools and will be expandable to facilitate imaging of the chest wall and axillae. Construction will be phased. At each stage we will use a continuous test/re-test approach using pre-calculated bench-marks to permit efficient and timely resolution of arising issues. We will employ state-of-the-art image reconstruction techniques using measured system models to maximize spatial resolution, and we will carefully implement all necessary data corrections for quantitative imaging. We will compare performance with whole-body PET/CT and MRI in a trial of 30 patients with known breast cancer. Health relatedness: Breast PET imagers tested in the clinic to date are low-cost, low -performance devices that cannot adequately assess the methodology in vivo, and do not provide 3D images fused with 3D anatomic information (a technique that is well- proven in the body). Thus the known power of molecular imaging in staging and re- staging, response to therapy studies and drug development is not available to a large fraction of women with primary breast cancer. The proposed device will solve this problem and allow the determination of the minimum imaging requirements for adequate clinical performance - a pre-requisite for translation of this technology into patient care. PUBLIC HEALTH RELEVANCE: Breast PET imagers tested in the clinic to date are low-cost, low -performance devices that cannot adequately assess the methodology in vivo, and do not provide 3D images fused with 3D anatomic information (a technique that is well- proven in the body). Thus the known power of molecular imaging in staging and re- staging, response to therapy studies and drug development is not available to a large fraction of women with primary breast cancer. The proposed device will solve this problem and allow the determination of the minimum imaging requirements for adequate clinical performance - a pre-requisite for translation of this technology into patient care.